Sulfation is common to a wide variety of organisms, from bacteria to eukaryotes, and it functions in a wide range of biological activities in the cell, i.e., cell-cell communication, cell growth, development, and protection. Sulfated polysaccharides exist in animals and in algae but not in terrestrial plants.
In nature, sulfation processes involve sulfotransferases (STs), a group of enzymes that catalyze the transfer of a sulfate group from the universal donor 3′-phosphoadenosine 5′-phosphosulfate (PAPS) to a variety of molecules—from low-molecular-weight hormones and xenobiotics to high-molecular-weight polysaccharides and proteins (Honke and Taniguchi, 2002).
STs are divided into two classes, cytosolic and membrane-associated. By virtue of their greater abundance in the cells and the ease with which they can be purified and assayed, cytosolic STs have been more thoroughly studied. Cytosolic STs catalyze the sulfation of small, hydrophobic molecules such as phenols and steroids, whereas the substrates of membrane-associated STs are hydrophilic polysaccharides, and protein. In addition, cytosolic STs can sulfate a wider variety of substrates than the more specific membrane-associated STs, which participate in biological processes such as molecular recognition, signal transduction and viral entry to the cell.
Most members of the ST family have similar structures. The PAPS-binding region is conserved at the amino acid level and contains the following structural motifs: a 5′-phosphosulfate-binding (5′-PSB) loop, a 3′-phosphate-binding (3′-PB) loop, and a β-strand-loop-α-helix (Chapman et al., 2004; Negishi et al., 2001). The largest variation among STs is found, as expected, in the substrate-binding region.
Most of what is known about ST enzymes is based on cytosolic STs, while the information of membrane-associated ST remains limited. Existing knowledge about membrane-associated STs comes mainly from animals, and so far no report has been published on STs from terrestrial plants or algae.
The cells of the red microalga Porphyridium sp. are encapsulated within a viscous sulfated polysaccharide, the external part of which dissolves into the growth medium. A complex heteropolymer (molecular mass 3-5×106 Da), this polysaccharide comprises about 10 monosaccharides, including the major sugars xylose, glucose, and galactose and the minor sugars mannose and methylated monosugars. The presence of glucuronic acid and sulfur esters, which constitute 3% of the molecule, make it anionic. This unique complex contains a non-covalently bound, 66-kDa glycoprotein that was identified as the main protein in the cell wall of Porphyridium sp. (Shrestha et al., 2004).
Sulfated polysaccharides play important roles in many biological processes. For example, the sulfated Lea tetra- and pentasaccharides are potent E-selectin inhibitors and sialyl Lewis x with a sulfate group at the 6-position of galactose is a ligand for L-selectin. These sulfated sugars play important roles, among others, in cell adhesion in response to inflammatory reactions. The sulfation of hydroxysteroids provides hydrophilic forms for excretion. Many glycosaminoglycans [GAGs] are sulfated and are involved in numerous cellular functions.